Bioequivalence

Abstract

Exposure in the central circulation is an essential prerequisite for efficacy and safety of systemic drugs. After oral administration the rate and extent of absorption from the gastrointestinal tract may be significantly determined by the biopharmaceutical properties of both, the drug substance as well as the drug formulation. This is the reason why rate and extent of bioavailability of oral dosage forms needs to be characterized thoroughly during drug product development for regulatory submission. In case of generic medicinal products assessment of bioequivalence in comparison to an appropriate reference product is the basis for marketing authorization applications and the approval process. The requirements for this procedure are therefore clearly defined in the bioequivalence guidelines published by the competent regulatory authorities, e.g. EMA in Europe or FDA in the USA.

Most relevant parameters to be considered in this context are discussed in this chapter. Since there are still certain differences between the main guidelines activities have been started to discuss the basis for science-driven regulations and to harmonize the existing requirements. In particular the Global Bioequivalence Harmonization Initiative (GBHI) of the European Federation for Pharmaceutical Sciences (EUFEPS) has achieved significant contributions to this process.